[Ricardo]

Velcade after "mini" allo transplants

by Ricardo on Thu Aug 09, 2012 12:11 pm

Hi everyone,

Preventing GVHD after allo transplants seems to be getting more attention among myeloma researchers these days. There's a new study out in the Journal of Clinical Oncology that suggests that a short course of Velcade treatment after a mini (reduced intensity conditioning, or "RIC") allogeneic transplant may reduce graft versus host disease and improve patient survival.

Here's a link to the study:

http://jco.ascopubs.org/content/early/2012/08/06/JCO.2012.42.0984.abstract

The trial involved patients with "hematologic malignancies" getting mini allo transplants from HLA-mismatched donors. I believe that, normally, the outcomes of such transplants are not as good as those carried out with HLA-matched donors.

However, the authors found that the results in their trial, which involved giving the patients several treatments of Velcade after the transplant, yielded results similar to those seen in patients with HLA-matched donors.

Here is the study title and abstract information:

Title:
Bortezomib-Based Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Transplantation

Authors:
John Koreth⇓, Kristen E. Stevenson, Haesook T. Kim, Sean M. McDonough, Bhavjot Bindra, Philippe Armand, Vincent T. Ho, Corey Cutler, Bruce R. Blazar, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz and Edwin P. Alyea III

Abstract

Purpose: HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell transplantation (HSCT) is associated with increased graft-versus-host disease (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory properties potentially beneficial for control of GVHD in T-cell-replete HLA-mismatched transplantation.

Patients and Methods: We conducted a prospective phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib, administered once per day on days +1, +4, and +7 after peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients: 40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up.

Results: The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI, 16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively. Two-year progression-free survival and overall survival were 51% (95% CI, 36% to 64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our institution. Immune recovery, including CD8+ T-cell and natural killer cell reconstitution, was enhanced with bortezomib.

Conclusion: A novel short-course, bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC HSCT, can enhance early immune reconstitution, and appears to be suitable for prospective randomized evaluation.